title: Putting poly (ADP-ribose) polymerase and other DNA repair inhibitors into clinical practice.
abstract: OBJECTIVE
  Poly (ADP-ribose) polymerase (PARP) and other DNA repair inhibitors are currently tested in numerous clinical trials, with variable success. Inhibitors are used in monotherapy, for example, PARP inhibitors in BRCA mutated cancers, or more widely in combination treatments. DNA repair inhibitors have, as chemotherapy, great potential for long-term disease control, or potentially even cures. However, the design of clinical trials using DNA repair inhibitors is intricate, as these inhibitors may also potentiate normal tissue toxicity without improving overall disease control.
  
  
  RESULTS
  Recent findings of mechanism of action of PARP inhibitors and other DNA repair inhibitors are presented, and how the underlying genetic background and interplay between DNA repair pathways influence the choice of tumour location and combination strategies. The hallmark of individualized cancer therapy is to be able to genetically distinguish the responding subclass of cancer patients, and it is widely used when targeting oncogenes. The PARP inhibitors in BRCA mutated cancers also demonstrate that this approach is possible in a synthetic lethal context.
  
  
  CONCLUSIONS
  There is strong proof-of-concept for DNA repair inhibitors being a useful anticancer strategy in well designed clinical trials.
authors.affiliation: Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D057285:Precision Medicine; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases